This month, I will be covering some of the data from this year’s American Society of Clinical Oncology^® (ASCO) meeting. In this edition, I will review a number of the abstracts in melanoma, gynecologic oncology, genitourinary cancers, and breast cancers.

Presentations from the Gynecologic Cancer Session at The Annual Oncology Meeting

Abstract 1: A randomized trial in ovarian cancer (OC) of early treatment of relapse based on CA125 level alone versus delayed treatment based on conventional clinical indicators (MRC OV05/EORTC 55955 trials).

Rustin et al, in the first plenary session presentation, presented the results of the randomized trials MRCOV05 and EORTC 55955 that evaluated the early treatment of relapsed ovarian cancer based on CA125 level alone versus delayed treatment based on conventional clinical indicators. As an introduction, 80% of patients with advanced ovarian cancer will relapse after first-line chemotherapy. Serial measurement of CA125 has the potential for earlier detection of relapse. However, it has been unclear whether patients benefit from earlier treatment of relapse. The trial randomized 529 women in complete clinical remission after first-line platinum based therapy and a normal CA125. If the CA125 rose to over 2-times the upper limit of normal, the patients were randomized to early treatment, where both the clinician and patient were informed, or to delayed treatment, where the clinician was not informed and treatment was delayed until clinically indicated. The primary outcome measure was OS, with secondary outcomes being time to second-line treatment, time to third-line treatment or death, and quality of life. The study was designed to detect a 10% improvement in 2-year OS in the immediate treatment arm. Results: With a median follow-up of 49 months and a total of 351 deaths, there was no evidence of a difference in OS between the immediate and delayed arms. In the early treatment arm based on the rise in CA125 second-line chemotherapy started a median of 4.8 months earlier, and third-line chemotherapy started a median of 4.6 months earlier. In addition, early chemotherapy did not improve quality of life. How should this trial influence practice? Women can be reassured that:

1. There is no benefit from early detection of relapse by routine CA125 measurements
2. Even if the CA125 rises, chemotherapy can be delayed until signs or symptoms of tumor recurrence.

Abstract 5504: Influence of residual disease and extreme drug resistance assays on outcome in patients with epithelial ovarian cancer.

Karam et al presented data from this retrospective study. As a background, extreme drug resistance (EDR) assays have been used as tools identifying chemotherapy agents that are least likely to be of clinical benefit. They have never shown the ability to predict which drugs will work. The study performed a retrospective review of 377 epithelial ovarian cancer patients at the Cedars Sinai Medical Center in Los Angeles. Extreme drug resistance assays were assessed between 1995 and 2005. The endpoints were time to first recurrence, OS, and survival after recurrence. A multivariate analysis was performed for prognostic characteristics and included in the EDR assay. The following characteristics were associated with a worse survival:

1. Increasing age as measured in decades
2. Microscopic residual disease comparing 0.1 – 1.0 cm to >1.0 cm.

However, EDR assay for single agents or combinations did not independently predict patient outcomes.

Three separate studies were reported evaluating different chemotherapy regimens in both the front-line and at the time of relapse for epithelial ovarian cancer.

Abstract LBA5510: A randomized, phase III study (AGO-OVAR-9, GINECO-TCG, NSGO-OC-0102): Gemcitabine-paclitaxel-carboplatin (TCG) versus paclitaxel-carboplatin (TC) as first-line treatment of ovarian cancer (OC): Survival of FIGO stage I-IIA patients.

Herrstedt et al presented data from a randomized phase III in first-line treatment of ovarian cancer in International Federation of Gynecology and Obstetrics (FIGO) stage I-IIA patients. In this trial, 1742 patients with FIGO IC – IV were randomly assigned to 1 of the 2 arms, each given for 6 cycles. The primary statistical endpoint was PFS. The TCG regimen was more toxic with regards to grade 3/4 toxicities with greater anemia, thrombocytopenia, leucopenia, febrile neutropenia. A prior interim analysis had shown that addition of gemcitabine to TC did not improve OS in patients with FIGO stage IIB-IV disease. Approximately 11% of the patients in the trial (n = 175) had FIGO I-IIA disease. However, even in the lower stage patients, the addition of gemcitabine to TC did not improve efficacy in these patients, and if anything, there was a negative trend for survival. The authors concluded that the addition of gemcitabine to TC in patients with their initial diagnosis of ovarian cancer cannot be recommended.

Abstract LBA5508: Carboplatin plus paclitaxel (CP) versus carboplatin plus stealth liposomal doxorubicin (CLD) in patients with advanced ovarian cancer (AOC): Activity and safety results of the MITO-2 randomized multicenter trial.

Pignata and colleagues presented the results of the MITO-2 trial evaluating the activity and safety of carboplatin-paclitaxel (CP) versus carboplatin-liposomal doxorubicin (CLD). In this trial, 820 women with stage IC-IV epithelial ovarian cancer were randomly assigned to 1 of the 2 chemotherapy regimens, both for 6 cycles. The primary endpoint was PFS. Results: With a median follow-up of 35 months, 530 events for PFS, and 269 deaths were recorded. The ORR was 59% with CP and 57% with CLD. There were no differences in PFS or OS between the 2 chemotherapy groups. There were significant differences in toxicity with CLD showing more anemia, and thrombocytopenia, skin toxicity, and stomatitis. Patients receiving CP exhibited more diarrhea, hair loss, and neurotoxicity.

With the results of these 2 phase III front-line trials, how will this affect the current standard of care, which is the use of carboplatin and paclitaxel? Essentially, there is no current role for the addition of gemcitabine. And for patients for whom one needs to avoid a neurotoxic drug, liposomal doxorubicin can be substituted for paclitaxel. The current Gynecologic Oncology Group (GOG) trial accruing patients in the US is GOG 218 that is randomizing stage III-IV suboptimally cytoreduced patients to 1 of 3 arms:

1. Carbo-paclitaxel x 6
2. CP + bevacizumab x 6
3. CP + bevacizumab x 6 followed by maintenance bevacizumab until progression.

The third ovarian chemotherapy trial presented that I will be discussing was in women with relapsed, platinum-sensitive ovarian cancer.

Abstract LBA5509: A randomized, phase III study of carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in relapsed platinum-sensitive ovarian cancer (OC): CALYPSO study of the Gynecologic Cancer Intergroup (GCIG).

Pujade-Lauraine and colleagues presented data from the CALYPSO trial which that was a phase III trial comparing carboplatin-pegylated liposomal doxorubicin (CD) versus carboplatin-paclitaxel (CP). In this trial, 976 women with ovarian cancer in late relapse (>6 months) after first-line or second-line platinum-based therapy were randomized to 6 cycles of 1 of the 2 therapies. Progression-free survival was reported at 11.3 months for the CD arm and 9.4 months for the CP arm with a hazard ratio of 0.82 and a P value of .005. The OS data was immature with only 322 deaths to date. Carboplatin-paclitaxel was associated with more severe toxicity, including carboplatin hypersensitivity, alopecia, and long-lasting neuropathy. Moderate reversible hand-foot syndrome, mucositis, and nausea/vomiting were more frequent with CD. The authors concluded that carboplatin-pegylated liposomal doxorubicin offers an evidence-based option for patients with platinum-sensitive recurrent ovarian cancer.

Cervical cancer is the second-most common cancer among women worldwide. The current standard therapy for locally advanced cancer of the cervix consists of external beam radiation with concurrent cisplatin.

Abstract CRA5507: A phase III study comparing concurrent gemcitabine (Gem) plus cisplatin (Cis) and radiation followed by adjuvant Gem plus Cis versus concurrent Cis and radiation in patients with stage IIB to IVA carcinoma of the cervix.

Dueñas-González et al presented the results phase III randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant this phase III trial. The trial enrolled 515 women with the primary statistical endpoint being PFS at 3 years. Those randomized to arm A received cisplatin 40 mg/m² + gemcitabine 125 mg/m² IV weekly for 6 weeks with concurrent pelvic radiation therapy. They then received adjuvant chemotherapy with 2 cycles of cisplatin 50 mg/m² day 1 and gemcitabine 1 gm/m² days 1 and 8 given every 3 weeks. Patients on arm B received cisplatin 40 mg/m² weekly for 6 weeks with concurrent external beam radiation. They received no adjuvant chemotherapy. Local failure was reduced from 16.4% to 11.2% with the addition of gemcitabine. Distant failure was also reduced by 55% from 16.4% to 8.1%. Progression-free survival at 3 years was 74.4% for arm A vs 65% for arm B (P = .029). In addition, OS was statistically superior with the addition of gemcitabine (78.2% vs 69.1%). The authors concluded that when compared with the current standard of care, inclusion of gemcitabine significantly improves survival outcomes for patients with locally advanced cervical cancer at the expense of increased, but clinically acceptable and manageable toxicity. Further studies are required to define the optimal application of this regimen and to delineate the relative contributions of multi-agent chemoradiation and adjuvant chemotherapy to survival outcomes and toxicity.

OncoFacts™ Editor:

Christy Russell, MD

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